1. Pathology and Pathogenesis of Gallstones & Cholecystitis
Dr. Mamlook Elmagraby

2. Objectives of the lecture:
Upon completion of this lecture, students should be able to:
Compare the various types of gallstones, how they are formed, what the risk factors for their development are, and what complications they can cause
Describe the different types of cholecystitis
Recognize the predisposing factors of cholecystitis
Understand the pathogenesis of acute and chronic cholecystitis

3. Cholelithiasis (Gallstones)

4. Cholelithiasis (Gallstones)
Gallstones affect 10% to 20% of adult populations in developed countries
The majority of gallstones are silent, and most individuals remain free of biliary pain or other complications for decades
There are two main types of gallstones:
Cholesterol stones (90%) containing more than 50% of crystalline cholesterol monohydrate
The rest are pigment stones composed predominantly of bilirubin calcium salts

5. Cholesterol Stones Pigment Stones Advancing age Female sex hormones
Female gender
Oral contraceptives
Pregnancy
Obesity and metabolic syndrome
Rapid weight reduction
Gallbladder stasis
Inborn disorders of bile acid
metabolism
Hyperlipidemia syndromes   
Pigment Stones
Chronic hemolytic syndromes
Biliary infection
Risk Factors for Gallstones

6. Cholelithiasis (Gallstones)
Pathogenesis
Cholesterol Stones.
Four conditions contribute to formation of cholesterol gallstones:
Supersaturation of bile with cholesterol
Hypomotility of the gallbladder
Accelerated cholesterol crystal nucleation
Hypersecretion of mucus in the gallbladder

7. Cholelithiasis (Gallstones)
Pigment Stones
They are complex mixtures of:
Abnormal insoluble calcium salts of unconjugated bilirubin
Inorganic calcium salts
Factors increase the risk of developing pigment stones:
↑ Levels of unconjugated bilirubin in bile (hemolytic syndromes)
Bacterial contamination of the biliary tree
Severe ileal dysfunction or bypass

8. Cholelithiasis (Gallstones)
Morphology
Cholesterol stones
Cholesterol stones arise in the gallbladder
Pure cholesterol stones are pale yellow, round to ovoid
↑ proportions of calcium carbonate, phosphates, bilirubin → discoloration (gray-white to black)
Most often, multiple stones are present
The majority are radiolucent

9. Cholesterol stone and cholesterolosis of the gallbladder - Gross, mucosal surface
This image shows a round, yellow, pure cholesterol gallstone next to an opened gallbladder, which shows a yellow mucosal surface caused by cholesterolosis (deposits of cholesterol in tissue) of the gallbladder.

10. Cholelithiasis (Gallstones)
“Black” pigment stones.
rarely >1.5 cm in diameter
They are present in great number
They crumble to the touch
50% to 75% are radiopaque
“Brown” pigment stones.
Soft and laminated & greasy consistency
Stones, which contain calcium soaps, are radiolucent

11. Gallstones, pigment stones - Gross
These minute black stones are pure pigment stones.
Theyare present in large numbers

12. Cholelithiasis (Gallstones)
Clinical Features
Gallstones develop in 10% to 20% of Americans
Between 50% and 60% of these individuals remain asymptomatic
One third develop biliary colic or chronic cholecystitis
15% develop acute complications
Symptoms arise from:
Contraction of the gallbladder during transient obstruction of the cystic duct by gallstones
Persistent obstruction of the cystic duct leads to superimposed inflammation or infection of the gallbladder(acute cholecystitis)

13. Cholelithiasis (Gallstones)
Obstruction by gallstones can occur at the level of the:
Cystic duct
Common hepatic duct
Common bile duct
Ampulla of Vater
Factors that may predict the presence of choledocholithiasis include jaundice, pancreatitis, abnormal liver test results, bile duct dilation
Obstruction of the distal common bile duct may result in abdominal pain, cholangitis, or pancreatitis

14. Natural history of asymptomatic gallstones
Natural history of asymptomatic gallstones. A, The clinical syndromes associated with gallstones are shown, and the numbers represent
the approximate percentage of adults who develop one or more of these symptoms or complications over a 15- to 20-year period. Over this
period, about 30% of individuals with gallstones undergo surgery. (The risk for developing complications of gallstones varies considerably among
series. The figures shown represent those derived from more recent studies.) B, Clinical manifestations of symptomatic gallstones. Locations of blockages
associated with various conditions are indicated

15. Cholelithiasis (Gallstones)
Biliary colic refers to the group of symptoms experienced when the gallbladder contracts against outlet obstruction Gallstones are best demonstrated by transabdominal ultrasonography Laparoscopic cholecystectomy has replaced open cholecystectomy as the treatment of choice for recurrent biliary pain

16. Clinical and pathologic effects of cholelithiasis
Ileus is a partial or complete non-mechanical blockage of the small and/or large intestine
There are two types of intestinal obstruction, mechanical and non-mechanical.
Mechanical obstructions occur because the bowel is physically blocked and its contents can not pass the point of the obstruction. This happens when the bowel twists on itself (volvulus) or as the result of hernias, impacted feces, abnormal tissue growth, or the presence of foreign bodies in the intestines.
Non-mechanical obstruction, called ileus or paralytic ileus, occurs because peristalsis stops

17. Cholecystitis

18. Acute Cholecystitis Acute calculous cholecystitis
Acute cholecystitis refers to distention, edema, ischemia, inflammation, and secondary infection of the gallbladder
Acute calculous cholecystitis
It is an acute inflammation of the gallbladder, triggered by obstruction of the neck or cystic duct
It frequently develops in diabetic patients
Acute acalculous cholecystitis
Cholecystitis without gallstones
It may occur in severely ill patients

19. Acute Cholecystitis Pathogenesis Acute calculous cholecystitis
Chemical irritation of the obstructed gallbladder
The protective glycoprotein mucus layer is disrupted
Prostaglandins contribute to inflammation
Gallbladder dysmotility
Increased intraluminal pressure compromise blood flow to the mucosa
Later in the course bacterial contamination may develop

20. Acute Cholecystitis Acute acalculous cholecystitis:
It may result from ischemia
Contributing factors:
Inflammation and edema of the wall
Gallbladder stasis
Biliary sludge
Primary bacterial infection

21. Acute Cholecystitis
Risk factors in acute acalculous cholecystitis include (seriously ill patients):
Sepsis with hypotension and multisystem organ failure
Immunosuppression
Major trauma and burns
Diabetes mellitus
Infections

22. Acute Cholecystitis Morphology
The gallbladder is usually enlarged and having a bright red to green-black discoloration
The serosal covering is coated by fibrin or suppurative exudate
In calculous cholecystitis:
An obstructing stone is present in the neck of the gallbladder or the cystic duct
The lumen is filled with turbid bile that may contain large amounts of fibrin, pus, and hemorrhage

23. Acute Cholecystitis Clinical Features
The characteristic feature of acute cholecystitis is the acute onset of upper abdominal pain that lasts for several hours
The pain gradually increases in severity and localizes to the epigastrium or right hypochondrium
The pain radiate to the right lumbar, scapular, and shoulder area
Nausea and vomiting, anorexia, and low-grade fever are common
Unlike biliary pain, the pain of acute cholecystitis does not subside spontaneously

24. Acute Cholecystitis
Complications of acute cholecystitis include emphysematous cholecystitis, empyema, gangrene, perforation of the gallbladder Ultrasound has emerged as the initial test of choice Because of the high risk for recurrent acute cholecystitis, most patients need to undergo cholecystectomy Antibiotics are used when fever or leukocytosis is present

25. Chronic Cholecystitis
An evolving inflammatory process, caused by repeated episodes of low-grade gallbladder obstruction over a period of days to years resulting in recurrent mucosal trauma and inflammation
Chronic cholecystitis is a term used to describe chronic inflammatory cell infiltration of the gallbladder on histopathology
Gallstones are the causative agent in most patients
In 12% of patients with chronic cholecystitis, there are no demonstrable stones

26. Chronic Cholecystitis
Morphology
Gross changes
Dense fibrous adhesions, subserosal fibrosis, thickened wall
The lumen contains clear, green-yellow, mucoid bile & stones
Histological changes:
Mononuclear cell infiltration
Subepithelial and subserosal fibrosis
Extensive dystrophic calcification within the gallbladder wall (Porcelain gallbladder, with increased risk of cancer)

27. Gallbladder, cholelithiasis and acute and chronic cholecystitis - Gross
This case of acute and chronic cholecystitis shows marked fibrous thickening of the wall of the gallbladder.
The mucosal surface is erythematous and is also ulcerated in the regions of the neck and fundus of the gallbladder due to impaction of a large gallstone (cholelithiasis)

28. Chronic Cholecystitis
Clinical Features
The symptoms are those of biliary colic without clinical features of acute cholecystitis
It is characterized by recurrent attacks of colicky abdominal pain
Nausea, vomiting, intolerance for fatty foods are frequent
Transabdominal ultrasound is the best initial test
The treatment is laparoscopic cholecystectomy